Diisopropylethylamine → (E)-6-{2-[methyl-(3-methyl-benzo[b]thiophen-2-ylmethyl)carbamoyl]vinyl}-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester

HRID 1362309Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1362309
[CH3:1][N:2]([CH2:7][C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[C:9]=1[CH3:17])[C:3](=[O:6])[CH:4]=[CH2:5].[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](Br)=[CH:28][N:27]=2)=[O:22])[CH3:19].CCN(C(C)C)C(C)C>C(C#N)C.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](/[CH:5]=[CH:4]/[C:3](=[O:6])[N:2]([CH3:1])[CH2:7][C:8]1[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[C:9]=1[CH3:17])=[CH:28][N:27]=2)=[O:22])[CH3:19]

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 17930139N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamideHCID 53396436Ethyl 6-bromo-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate

Produkt 1

HCID 59277530(E)-6-{2-[methyl-(3-methyl-benzo[b]thiophen-2-ylmethyl)carbamoyl]vinyl}-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl esterAusbeute 56,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 7854PropionitrileLösungsmittel

Versuchsvorschrift

A suspension of N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide (500 mg, 2.04 mmol), 6-bromo-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester (665 mg, 2.24 mmol), (o-tol)3P (135 mg, 0.44 mmol) and DIEA (0.4 mL, 2.45 mmol) in EtCN (10 mL) and DMF (10 mL) was deoxygenated with argon for 30 min. Pd(OAc)2 (50 mg, 0.22 mmol) was added, the mixture was deoxygenated with argon for 20 min and then heated to reflux overnight. The mixture was cooled to room temperature and concentrated. The residue was partitioned between CH2Cl2 and H2O. The organic layer was washed with satd NaCl, dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH) gave the title compound (530 mg, 56%) as a yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.98 (d, J=2.1 Hz, 1H), 8.67 (s, 1H), 8.44-8.42 (m, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.75-7.52 (m, 2H), 7.43-7.31 (m, 3H), 5.14-4.91 (m, 2H), 4.32-4.25 (m, 2H), 3.18-2.96 (m, 3H), 2.43 (s, 3H), 1.33-1.27 (m, 3H); MS (ESI) m/e 462 (M+H)+.

Aufarbeitung

  1. customwas deoxygenated with argon for 30 min
  2. customthe mixture was deoxygenated with argon for 20 min
  3. temperatureheated
  4. temperatureto reflux overnight
  5. concentrationconcentrated
  6. customThe residue was partitioned between CH2Cl2 and H2O
  7. washThe organic layer was washed with satd NaCl
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-fd1a798563554238b62ed7c551547be2
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879872B2

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